Structure of promoter-bound TFIID and model of human pre-initiation complex assembly

Nature. 2016 Mar 31;531(7596):604-9. doi: 10.1038/nature17394. Epub 2016 Mar 23.

Abstract

The general transcription factor IID (TFIID) plays a central role in the initiation of RNA polymerase II (Pol II)-dependent transcription by nucleating pre-initiation complex (PIC) assembly at the core promoter. TFIID comprises the TATA-binding protein (TBP) and 13 TBP-associated factors (TAF1-13), which specifically interact with a variety of core promoter DNA sequences. Here we present the structure of human TFIID in complex with TFIIA and core promoter DNA, determined by single-particle cryo-electron microscopy at sub-nanometre resolution. All core promoter elements are contacted by subunits of TFIID, with TAF1 and TAF2 mediating major interactions with the downstream promoter. TFIIA bridges the TBP-TATA complex with lobe B of TFIID. We also present the cryo-electron microscopy reconstruction of a fully assembled human TAF-less PIC. Superposition of common elements between the two structures provides novel insights into the general role of TFIID in promoter recognition, PIC assembly, and transcription initiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Cryoelectron Microscopy
  • DNA / chemistry
  • DNA / metabolism
  • DNA / ultrastructure
  • Humans
  • Models, Molecular
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • Substrate Specificity
  • TATA Box / genetics
  • TATA-Binding Protein Associated Factors / chemistry
  • TATA-Binding Protein Associated Factors / metabolism
  • TATA-Binding Protein Associated Factors / ultrastructure
  • TATA-Box Binding Protein / chemistry
  • TATA-Box Binding Protein / metabolism
  • TATA-Box Binding Protein / ultrastructure
  • Transcription Factor TFIIA / chemistry
  • Transcription Factor TFIIA / metabolism
  • Transcription Factor TFIIA / ultrastructure
  • Transcription Factor TFIID / chemistry
  • Transcription Factor TFIID / metabolism*
  • Transcription Factor TFIID / ultrastructure*
  • Transcription Initiation, Genetic*

Substances

  • TATA-Binding Protein Associated Factors
  • TATA-Box Binding Protein
  • Transcription Factor TFIIA
  • Transcription Factor TFIID
  • DNA

Associated data

  • PDB/5FUR